title: Lewis and secretor gene dosages affect CA19-9 and DU-PAN-2 serum levels in normal individuals and colorectal cancer patients.
abstract: The effect of doses of the secretor (Se) and Lewis (Le) genes on the serum levels of CA19-9 and DU-PAN-2 was investigated in 400 normal individuals. It was clearly demonstrated that the Se gene dosage negatively affected both the CA19-9 and DU-PAN-2 values, whereas the Le gene dosage positively affected the CA19-9 value and negatively affected the DU-PAN-2 value. The 400 normal individuals were separated into nine groups by their Le and Se genotypes, as follows: group 1, Le/Le and se/se; group 2, Le/le and se/se; group 3, Le/Le and Se/se; group 4, Le/le and Se/se; group 5, Le/Le and Se/Se; group 6, Le/le and Se/Se; group 7, le/le and se/se; group 8, le/le and Se/se; and group 9, le/le and Se/Se. The group 1 individuals, having homozygous inactive Se alleles (se/se) and homozygous active Le alleles (Le/Le), exhibited the highest mean CA19-9 value. The CA19-9 value clearly ranged from a high in group 1 to a low in group 9. All of the Le-negative individuals who had the le/le genotype (groups 7, 8, and 9) had completely negative CA19-9 values, i.e., under 1.0 unit/ml, irrespective of the Se genotype. Group 7 individuals (le/le and se/se) showed a higher mean DU-PAN-2 value than did individuals in other groups. The Le-negative individuals in groups 8 and 9 also showed a higher mean DU-PAN-2 value than did the Le-positive individuals in groups 1-6. We recommend that the revised Le and Se genotype-dependent positive/negative cutoff values for CA19-9 and DU-PAN-2, determined in this study, be applied for more accurate cancer diagnoses. The Le and Se genotypes of 168 patients with colorectal cancer were also examined, and the CA19-9 and DU-PAN-2 values were measured before surgical resection. All 15 Le-negative patients (le/le) with colorectal cancer again showed undetectable CA19-9 values, i.e., under 1.0 unit/ml, but many of them exhibited highly positive DU-PAN-2 values. In contrast, many of the Le-positive patients (Le/Le or Le/le) had positive CA19-9 values, whereas very few of them exhibited positive DU-PAN-2 values. CA19-9 measurement is more useful than is DU-PAN-2 measurement for Le-positive patients, but it is not useful for Le-negative ones. DU-PAN-2 measurement should be performed in Le-negative patients for cancer diagnosis.
authors.affiliation: Division of Cell Biology, Institute of Life Science, Soka University, Hachioji, Toyko, Japan. hisashi@scc1.t.soka.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Narimatsu
authors.forename: H
authors.initials: H
authors.lastname: Iwasaki
authors.forename: F
authors.initials: F
authors.lastname: Nakayama
authors.forename: Y
authors.initials: Y
authors.lastname: Ikehara
authors.forename: T
authors.initials: T
authors.lastname: Kudo
authors.forename: S
authors.initials: S
authors.lastname: Nishihara
authors.forename: K
authors.initials: K
authors.lastname: Sugano
authors.forename: H
authors.initials: H
authors.lastname: Okura
authors.forename: S
authors.initials: S
authors.lastname: Fujita
authors.forename: S
authors.initials: S
authors.lastname: Hirohashi
mesh_terms: D000483:Alleles; D000951:Antigens, Neoplasm / Q000097:blood* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood* / Q000378:metabolism; D018395:CA-19-9 Antigen / Q000097:blood* / Q000378:metabolism; D002240:Carbohydrate Sequence; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics; D000939:Epitopes / Q000235:genetics / Q000378:metabolism; D005647:Fucosyltransferases / Q000235:genetics*; D018628:Gene Dosage; D005838:Genotype; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000097:blood* / Q000378:metabolism; D010641:Phenotype; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D000939:Epitopes; D005647:Fucosyltransferases; D009363:Neoplasm Proteins; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C042317:DU-PAN-2 antigen, human; C019818:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase